Expert Insight

global update on the cell and gene therapy regulatory landscape

In support of the combined efforts by the European Commission (EC), the European Medicines Agency (EMA) and national competent authorities (NCA) to adapt and improve the regulatory framework to the development and patient access to Advanced Therapy Medicinal Products (ATMPs), the Alliance for Regenerative Medicine (ARM) has worked with its members to identify some of the main regulatory hurdles and potential solutions that would facilitate the development of ATMPs in Europe. A series of position papers have been published in 2017-2018 to outline ARM recommendations. Hospital exemption and GMO requirements for clinical trials with gene therapies have been identified as major obstacles for ATMP developers due to divergent interpretations and implementations by NCA. Other potential improvements in the regulatory framework include a convergence between the different Member States of donor testing and procurement requirements for cells and tissues used as starting materials for the manufacturing of ATMPs, a pragmatic approach with licensing requirements and regulatory processes, and a greater engagement and coordination in Europe for the development of international standards. ARM calls for pan-European convergence of requirements and, for each of the major issues identified, has defined recommendations for implementation by the EC, EMA or NCA to ensure faster patients access to these transformative medicines without compromising safety and efficacy aspects.

EXPERT INSIGHT

Simon Bishop, Simone Flight and Natalie Thomas

global update on the cell and gene therapy regulatory landscape

Early phase clinical development of cell based therapies in Australia can benefit from an abbreviated regulatory approval pathway, requiring limited resource burden relative to a European clinical trial application (CTA) or US Investigational New Drug application (IND), resulting in more rapid clinical trial initiation. With data that are generated in accordance with International Council for Harmonisation of Technical Requirements for Human Use (ICH) Good Clinical Practice (GCP), technical expectations in keeping with ICH/EU/US requirements, adherence to Pharmaceutical Inspection Co-operation Scheme (PIC/S) guidance (while requiring Good Manufacturing Practice (GMP)-like investigational product), and a government funded research and development (R&D) cashback scheme that can see tax offsets of up to 43.5%, Australia represents a highly cost-effective and efficient location for generation of clinical data that are valid for use in regulatory submissions in key jurisdictions.

Expert Insight

Xiaofei Wang, Wilson W Bryan and Lei Xu

Global update on the cell and gene therapy regulatory landscape

A key responsibility of the US Food and Drug Administration (FDA) is to facilitate availability of innovative, safe, and effective treatments to patients. The FDA utilizes several expedited programs to speed development of exceptionally promising therapies for serious or life-threatening conditions. The newest expedited programs are the Breakthrough Therapy Designation (BTD) and the Regenerative Medicine Advanced Therapy (RMAT) designation. The marketing approvals in 2017 of three gene therapy products with BTD represent the success of the BTD program. The 21st Century Cures Act (Cures Act) defines regenerative medicine therapy and creates the RMAT designation, bringing hope for earlier availability of new regenerative medicine therapies, including cellular therapies and certain gene therapies. This article provides an overview of the BTD and RMAT designation programs, and a summary of the experience with these programs in FDA’s Office of Tissues and Advanced Therapies (OTAT) in FDA’s Center for Biologics Evaluation and Research (CBER).

Expert insight

Yoshiaki Maruyama, Masaki Kasai, Kazunobu Oyama & Kazuhiko Chikazawa

global update on the cell and gene therapy regulatory landscape

On April 2015, the Ministry of Health, Labour and Welfare notified the start of the SAKIGAKE designation system in Japan. SAKIGAKE is a system to put innovative medical products, including pharmaceuticals, medical devices and regenerative medical products from Japan into clinical use. Taking into account that treatment of dieases would benefit from the introduction of innovative medical products as soon as possible, development in Japan should be enhanced by implementing all relevant policies, so as to achieve the early practical application originates from Japan ahead of other countries. On November 2014, the Pharmaceutical Affairs Law was revised and renamed the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act (PMD Act). This Act provides the option of a new pathway to obtain conditional and time-limited approval for regenerative medical products. Giving patients better access to innovative medical products by providing the sponsor with generous regulatory and scientific support from an early development stage was also initiated in USA in 2012 (Breakthrough Therapy Designation system) and in the European Union in 2016 (PRIME; Piority Medicines). This review describes the SAKIGAKE designation system in Japan and highlights key considerations for developing regenerative medical products based on experience of the Pharmaceuticals and Medical Devices Agency (PMDA) in consultation and review.

Expert insight

Yaron Ramati

Global Update on the Cell & Gene Therapy Regulatory Landscape

The lengthening shadow of increase in health spending in the coming years is sharpening the minds of legislators, regulators and payers alike. The growing time-to-market, the rising costs in development of novel medicines, as well as the more basic drive to be ‘ahead of the game’, forces the industry and the legislators to rethink basic postulates of drug development. The global regulatory environment is undergoing major reshape, allowing patients early access to breakthrough technology and allowing industry opportunities for early access to market. Patient advocacy groups are incorporated in legislation discussions, and are brought into the room where industry and regulator discuss the clinical development of novel therapies. Earlier access to market allows smaller commercial companies to jump through the ‘death valley’ of drug development, reduce the traditional high investment risks in biotechnology, and ultimately provide more competition to big and well-established pharma giants.